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NCT02665143

A Randomized Trial of a Combination of Nintedanib/Placebo in Combination With Induction Chemotherapy for Patients With Refractory or First Relapse Acute Myeloid Leukemia

Completed Phase 2 Results posted Last updated 8 April 2022
What this trial tests

Phase 2 trial testing Nintedanib and AML induction in Relapsed/Refractory Acute Myeloid Leukemia in 25 participants. Completed in 30 March 2021.

Timeline
21 July 2016
Primary endpoint
8 March 2021
30 March 2021

Quick facts

Lead sponsorYale University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment25
Start date21 July 2016
Primary completion8 March 2021
Estimated completion30 March 2021
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Yale University

Who can join

18 and older, any sex, with Relapsed/Refractory Acute Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Count of Patients With Treatment-Emergent Adverse Events (Phase 1) Primary · 60 days

In the Phase 1 portion of the study, safety will be assessed after the inclusion of the first 6 patients, to analyze tolerance and adverse events occurring during this trial and will decide on any action to be taken. Safety will be evaluated according to NCI CTCAE V4 criteria. TEAE's were considered adverse events that occurred within 60 days of treatment initiation. The title of this outcome measure was adjusted when results were entered.

GroupValue95% CI
Nintedanib and AML Induction6
Complete Remission Rate (Phase 2) Primary · Up to 2 years

In Phase 2, the primary endpoint of complete remission rate will be based on IWG 2003 AML response criteria. This construct is an overall response composite and it will be assessed using the following metrics: Morphologic complete remission (CR): ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, \< 5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. (No requirements for marrow cellularity, hemoglobin concentration). Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be \< 1,000/mcl but \>500 mcl and/or platelet count \< 100

GroupValue95% CI
Nintedanib and AML Induction5
Nintedanib and AML Induction4
Nintedanib and AML Induction1
Nintedanib and AML Induction1
Incidence of Hematological Improvement (Phase 2) Secondary · Up to 2 years

Evaluation of hematological improvement will be assessed based on IWG MDS 2006 criteria. Due to differing pretreatment conditions of participants, response to treatment in this construct will be assessed in the following manner: Erythroid response (pretreatment \<11 g/dL) : Hgb increase at least by 1.5 g/dL. Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of below or equal to 9.0 g/dL pretreatment will count in the RBC transfus

Hematological Improvement Erythroid
GroupValue95% CI
Nintedanib and AML Induction3
Nintedanib and AML Induction13
Nintedanib and AML Induction3
Hematological Improvement Neutrophils
GroupValue95% CI
Nintedanib and AML Induction6
Nintedanib and AML Induction10
Nintedanib and AML Induction3
Hematological Improvement Platelet
GroupValue95% CI
Nintedanib and AML Induction6
Nintedanib and AML Induction10
Nintedanib and AML Induction3

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected for up to 60 days for Phase 1, up to 2 years for Phase 2. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nintedanib and AML Induction: Phase 1
Serious: 2/6 (33%)
Deaths: 0/6
Nintedanib and AML Induction: Phase 2
Serious: 8/19 (42%)
Deaths: 0/19

Serious adverse events (9 terms)

ReactionSystemNintedanib and AML Inducti…Nintedanib and AML Inducti…
Febrile neutropeniaBlood and lymphatic system disorders——
Alanine aminotransferase increasedInvestigations——
Thromboembolic eventVascular disorders——
Aspartate aminotransferase increasedInvestigations——
Heart failureCardiac disorders——
Pericardial effusionCardiac disorders——
SepsisInfections and infestations——
Skin and subcutaneous tissue disorders - OtherSkin and subcutaneous tissue disorders——
Infections and infestations - OtherInfections and infestations——
Other adverse events (136 terms — click to expand)

ReactionSystemNintedanib and AML Inducti…Nintedanib and AML Inducti…
DiarrheaGastrointestinal disorders——
White blood cell decreasedInvestigations——
Lymphocyte count decreasedInvestigations——
NauseaGastrointestinal disorders——
HyperglycemiaMetabolism and nutrition disorders——
HypoalbuminemiaMetabolism and nutrition disorders——
AnorexiaMetabolism and nutrition disorders——
FeverGeneral disorders——
Alanine aminotransferase increasedInvestigations——
Aspartate aminotransferase increasedInvestigations——
HypertensionVascular disorders——
Gastrointestinal disorders - OtherGastrointestinal disorders——
Alkaline phosphatase increasedInvestigations——
Abdominal painGastrointestinal disorders——
Infections and infestations - OtherInfections and infestations——
HyponatremiaMetabolism and nutrition disorders——
AnemiaBlood and lymphatic system disorders——
PainGeneral disorders——
Neutrophil count decreasedInvestigations——
HypocalcemiaMetabolism and nutrition disorders——
InsomniaPsychiatric disorders——
ConstipationGastrointestinal disorders——
VomitingGastrointestinal disorders——
Edema limbsGeneral disorders——
INR increasedInvestigations——
HypophosphatemiaMetabolism and nutrition disorders——
DizzinessNervous system disorders——
FatigueGeneral disorders——
Blood bilirubin increasedInvestigations——
Platelet count decreasedInvestigations——
HeadacheNervous system disorders——
CoughRespiratory, thoracic and mediastinal disorders——
Rash maculo-papularSkin and subcutaneous tissue disorders——
Sinus tachycardiaCardiac disorders——
ChillsGeneral disorders——
HypernatremiaMetabolism and nutrition disorders——
Pain in extremityMusculoskeletal and connective tissue disorders——
ProteinuriaRenal and urinary disorders——
DyspneaRespiratory, thoracic and mediastinal disorders——
HypokalemiaMetabolism and nutrition disorders——

Most-reported serious reactions: Febrile neutropenia, Alanine aminotransferase increased, Thromboembolic event, Aspartate aminotransferase increased, Heart failure, Pericardial effusion, Sepsis, Skin and subcutaneous tissue disorders - Other.

Data from ClinicalTrials.gov NCT02665143 adverse events section.

Sponsor's own description

The purpose of this study is to determine if a combination of nintedanib+ induction chemotherapy can be an effective strategy for patients where outcome of relapse/refractory acute myeloid leukemia (AML) is poor.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. What Does the Economic Burden of Acute Myeloid Leukemia Treatment Look Like for the Next Decade? An Analysis of Key Findings, Challenges and Recommendations.
    Forsythe A, Sandman K. · · 2021 · cited 16× · PMID 33981169 · DOI 10.2147/jbm.s279736

Verify or expand the search:

Other recruiting trials for Relapsed/Refractory Acute Myeloid Leukemia

Currently open trials in the same condition.

Other Yale University trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02665143.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing